The need to develop new chemical insect control agents that are safe, selective, biodegradable, and environmentally acceptable is widely recognized. Conventional pesticides may be toxic not only to pest insects, but also to beneficial insects and even to humans, due to their neurotoxic mode of action. In addition, the development of insect resistance and the environmental pollution due to the mass application of persistent synthetic pesticides have given rise to increased interest in alternate measures for the commercial control of insect pests. Alternatives can include the use of natural plant products, representing an immense array of chemical structure types, which may serve as sources of or models for pest control agents. The bioassay-guided investigation of higher plants, especially those observed to be resistant to insect attack in the field, can result in the detection and subsequent isolation and structure elucidation of potential pest control agents. Some natural plant products which have already been commercialized for use in insect control include the pyrethrins, rotenone, and nicotine and other alkaloids (Klocke, J.A. 1986. In "Allelochemicals: Role in Agriculture, Forestry, and Ecology." Waller, G. (ed.) ACS Symposium Series 330, American Chemical Society, Washington, D.C.). The search continues for still other useful plant products that will exhibit a selective toxicity towards pests combined with minimal adverse ecological and environmental impacts. Such compounds could find widespread commercial application in the agricultural, greenhouse and home garden supply markets.
The present invention includes a process of producing safe and novel insect control agents related to the naturally occurring plant compound salannin. Salannin is an insect antifeedant which disrupts the feeding and growth of susceptible insects and has the formula shown as 1a in Formula I. Antifeedant compounds are attractive in insect control since they are "biorational compounds" (i.e., they usually involve species-specificity and are generally neither persistent nor toxic). Traditional antifeedants have not been able to compete with conventional insecticides because they have been more expensive to produce and are capable of controlling only a narrow range of insect pests. We believe that the salannin derivatives described and claimed herein have a wider spectrum of activity (i.e., discourage more species of insects from feeding), will be effective in lower doses than formerly available antifeedants, and will be less expensive to produce commercially.
The inventions disclosed are derived from the tetranortriterpenoid salannin. Salannin occurs naturally in at least four species of Meliaceae: Azadirachta indica A. Juss (neem) (Henderson et al., Tetrahedron Lett. 1964 3969-3974; Henderson et al., Tetrahedron 1968 24:1525-1528), Melia dubia Cav. (de Silva et al., Phytochemistry 1969, 8: 1817-1819), Melia azedarach L. (chinaberry) (Srivastava, J. Nat. Prod. 1986, 49:56-61) and M. volkensii Gurke (Rajab et al., J. Nat. Prod. 1988, 51:168-171). The structure of salannin was proposed by Henderson et al. in 1964, and it is related to that of another highly potent insect antifeedant (and metamorphosis disrupter), azadirachtin (Zanno et al., J. Am. Chem. Soc. 1975, 97, 1975-1977; Kraus, W., in Chemistry and Biotechnology of Biologically Active Natural Products, edited by Szantay et al., Proc. Second Int. Conf. (Budapest, 1983) Elsevier; Amsterdam, New York, 1984: pp. 331-345.
Salannin acts as an antifeedant against the house fly (Musca domestica L.), California red scale (Aonidiella aurantii (Maskell)), locust (Loscusta spp.), Egyptian cotton leafworm (Spodoptera littoralis (Boisd.)), spiny bollworm (Earias insulana (Boisd.)), and the cucumber beetles Acalymma vittatum (F.) and Diabrotica undecimpunctata howardi (Warthen et al. 1978 U.S. Dept. Agric., Sci and Educ. Adm., Agric. Res. Results. Northeast. Ser., No. 2, 11 p. Beltsville, MD.; Warthen, 1979. U.S. Dept. Agric., Sci. and Educ. Adm., Agric. Rev. and Manuals, Northeast. Ser., No. 4, ARM-NE-4, 21 p. Beltsville, Md.; Meisner et al. 1981. Phytooarasitica 9, 27-32; Reed et al. 1982. J. Econ. Entomol. 75, 1109-1113.). We have also found antifeedant activity of salannin against the Colorado potato beetle (L. decemlineata).
The hereafter described and claimed salannin-derived antifeedants are "biorational" (Djerassem C., et al. 1974. Science 186, 596-607.) chemicals that are of relatively high selectivity for certain insects, low mammalian toxicity and biodegradable.
Although the insect antifeedant activity of salannin is documented, little is known about its structure-bioactivity relationships. Described and claimed herein are a number of derivatives of salannin which have greater antifeedant activity than the naturally-occurring salannin compound. Our work to establish chemical structure-activity relationships of salannin and derivatives as antifeedant compounds has shown that, for example, hydrogenation to the 2',3',20,21,22,23-hexahydrosalannin derivative increased the antifeedant activity of salannin against L. decemlineata at least eight-fold (from &gt;400 .mu.g/cm.sup.2 leaf disk to 25 .mu.g/cm.sup.2). Other derivatives show up to forty-fold greater activity over native salannin.